This study aimed to investigate the mechanism of compound Agrimonia pilosula enteritis capsules (CAPEC) on ulcerative colitis (UC) in mice with dampness-heat syndrome. The mice were randomly divided into five groups: the control group, the model group, the positive drug (5-aminosalicylic acid, 5-ASA) group, the low-dose CAPEC (CAPEC-L) group and the high-dose CAPEC (CAPEC-H) group. The mice models were established by using high-fat high-sucrose diet, feeding with distilled spirit and dextran sulfate sodium (DSS). The effects of CAPEC on bile acids (BAs) metabolic profiles in bile and the FXR-SREBP-1 signaling pathway were investigated in the model of UC in mice with dampness-heat syndrome by ELISA, qRT-PCR, UHPLC-QQQ/MS, and histopathological analysis. The results showed that, compared with the model group, the CAPEC-L group and the CAPEC-H group significantly reduced the disease activity index (DAI), and proinflammatory cytokine levels (including IL-6, IL-1β, and TNF-α) in both serum and colon tissues. Additionally, CAPEC markedly ameliorated intestinal inflammation, hepatic lipid accumulation, and pathological alterations in tongue tissue. The CAPEC-H group significantly attenuated the abnormal elevation of BAs profiles in bile, and up-regulated hepatic mRNA levels of Cyp7a1, Cyp7b1, Cyp27a1, Bsep, Fxr, and Shp, while down-regulating Srebp-1 and Cyp8b1 expression. The experimental results suggest that CAPEC alleviates UC with dampness-heat syndrome by ameliorating BAs metabolic disorders, hepatic lipid accumulation, and intestinal inflammation. These findings provide mechanistic insights into CAPEC’s traditional effects of clearing heat and drying dampness, and strengthening the spleen to relieve diarrhea.

ObjectiveTo investigate the trend and influencing factors of newly reported human immunodeficiency virus (HIV) positivity rate among men who had sex with men (MSM) in Shanghai from 2021 to 2024, and to provide evidence for formulating scientific prevention and control measures of AIDS. MethodsMultiple rounds of cross-sectional questionnaire surveys were conducted among MSM by Shanghai Qing’ai Health Promotion Center. Pearson and Cochran-Armitage trend χ² tests were used to analyze the differences and changes in population characteristics and newly reported HIV positivity rates. A logistic regression model was applied for multivariate analyses of factors associated with newly reported HIV positivity. ResultsA total of 1 653 MSM who had not been previously diagnosed with HIV infection were surveyed. The newly reported HIV positivity rates in 2021, 2023, and 2024 were 7.87%, 3.91%, and 3.06%, respectively, showing a decreasing trend (χ²_trend=13.460, P_trend<0.001). Multivariate analyses revealed that MSM aged 18‒<25 years, residing locally for <1 year, identifying as bisexual, lacking HIV knowledge, and having ≥10 same-sex partners in the past 6 months exhibited higher newly reported HIV positivity rates. Conversely, MSM knowledgeable about HIV prevention, residing locally for 1‒5 years, and engaging in oral sex with male partners in the past 6 months demonstrated lower HIV positivity rates. Annual analyses revealed that MSM with HIV knowledge had lower newly reported HIV positivity rates in 2023 and 2024 (aOR=0.300, 95%CI: 0.811‒0.111; aOR=0.202, 95%CI: 0.085‒0.483). ConclusionThe newly reported HIV positivity rate among MSM in Shanghai from 2021 to 2024 showed a decline. Future interventions should focus on young and mobile MSM, strengthen HIV knowledge education through platforms such as the internet, promote safe sexual behaviors and regular testing, and further expand the coverage of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) to control HIV transmission within this population.

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVE: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session, totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally, participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score, whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales. RESULTS: Following SMT treatment, pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1, TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise P<0.005; clusters >30; FDR correction). Additionally, the most substantial enhancement in ReHo values was observed for the Cuneus_R, while the most prominent reduction was noted for the Olfactory_R (voxelwise P<0.005; clusters >30; FDR correction). Moreover, a comparative analysis revealed that, in contrast to HCs, LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise P<0.005; clusters >30; FDR correction). Furthermore, the most significant enhancement in ReHo values was observed for Postcentral_L, while the most prominent reduction was identified for ParaHippocampal_L (voxelwise P<0.005; clusters >30; FDR correction). Notably, correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (r=0.9333, P<0.0001). CONCLUSIONS Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network, represented by the Cuneus_R, is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT06277739).
Humans ; Magnetic Resonance Imaging ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Brain/diagnostic imaging* ; Adult ; Manipulation, Spinal/methods* ; Middle Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management ; Rest ; Case-Control Studies

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective To investigate the therapeutic potential and prophylactic value of concomitant administration of nonsteroidal anti-inflammatory drug(NSAID)and antimicrobial agents in mitigating the incidence and severity of trauma-induced sepsis.Methods A retrospective cohort study encompassed the collection of clinical records from trauma patients managed in the department of intensive care unit(ICU)of Daping Hospital,Army Medical University(Third Military Medical University)from June 2008 to June 2024.Based on administered therapeutic protocols,patients were stratified into a control group(receiving antibiotic monotherapy)and a experimental group(undergoing adjunctive therapy with NSAID in conjunction with antimicrobial agents).Intergroup comparisons were performed to elucidate differences in baseline clinical characteristics and laboratory indices pertinent to therapeutic outcomes.Results A total of 268 trauma patients were included,with 72 patients in the control group and 196 patients in the experimental group.The majority of cases involved open trauma(67.5%)and injuries sustained from traffic accidents(44.0%),reflecting the principal mechanisms of injury.The respiratory tract was the most common site of infection(67.5%),with Acinetobacter baumannii(A.baumannii)emerging as the leading causative microorganism(18.0%).Among therapeutic agents,ibuprofen represented the most frequently employed NSAID(59.8%),whereas cephalosporins constituted the predominant class of antimicrobials(30.5%).Following intervention,the lymphocyte percentage(LYM%)was markedly elevated in the experimental group relative to control group[0.14(0.09,0.20)vs.0.12(0.09,0.15),P<0.01].In contrast,the levels of white blood cell count(WBC),neutrophil percentage(NEU%),D-dimer,glucose(Glu),and lactic acid(Lac)were significantly reduced[WBC(×109/L):8.82(6.36,12.96)vs.12.10(7.78,15.54);NEU%:0.76(0.67,0.81)vs.0.78(0.72,0.83);D-dimer(μg/L):2208.0(889.5,3301.5)vs.2943.9(1735.4,4997.6);Glu(mmol/L):6.8(6.2,7.9)vs.7.7(6.6,9.2);Lac(mmol/L):0.9(0.6,1.2)vs.1.1(0.8,1.5),all P<0.05].The experimental group demonstrated a significantly reduced incidence of traumatic sepsis compared with the control group[15.8%(31/196)vs.26.4%(19/72),P<0.05].Conclusion The combination of NSAID and antimicrobial agents exerts its protective effect by attenuating inflammatory and stress responses,reestablishing immune homeostasis,correcting coagulopathy,and enhancing tissue perfusion,thereby significantly decreasing the incidence of traumatic sepsis and contributing to improved prognostic outcomes in injured patients.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin,liquiritin apioside,verbascoside,narirutin,isoacteoside,apigetrin,hesperidin,isoliquiritin,ononin,liquiritigenin,glycyrrhizic acid,isoliquiritigenin,honokiol,obovatol,pogostone and magnolol in Jiawei Huoxiang Zhengqi Soft Capsules.METHODS The analysis was performed on a 40 ℃ thermostatic ZORBAX Eclipse Plus C18 column(2.1 mm×100 mm,1.8 μm),with the mobile phase comprising of 0.1％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r＞0.990 0),whose average recoveries were 83.74％-105.12％with the RSDs of 1.10％-4.8％.CONCLUSION This accurate,sensitive,stable and reproducible method can provide a reference for the overall quality control of Jiawei Huoxiang Zhengqi Soft Capsules.

Objective:To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.

Objective:To investigate the biomechanical correlation between ankle instability and osteochondral lesions of the talus (OLT) under loading conditionsMethods:A healthy 29-year-old male volunteer was selected for the study. A 64-slice spiral CT scan of the right lower limb was performed to construct a detailed finite element model of the ankle joint, including ligaments and cartilage. Three injury models were created: models of distal tibiofibular syndesmosis injury, lateral collateral ligament injury, and a combined injury of the distal tibiofibular syndesmosis and lateral collateral ligament. Differences in stress distribution on the tibiotalar joint surface, talus stress, and talus displacement were analyzed through anterior drawer test, inversion stress test, and external rotation stress test.Results:In the anterior drawer test, as the forward traction force increased (40, 60, 80, 100, 120, 140, and 150 N), all the injury models showed a progressive increase in tibiotalar joint surface stress, talus stress, and talus displacement. The combined injury model showed the highest tibiotalar joint surface stress (32.6 MPa), while the lateral collateral ligament injury model demonstrated the highest talus stress (56.5 MPa). Talus displacement increased significantly with traction, reaching the maximum (4.88 mm) in the combined injury model under 150 N. In the inversion stress test, stress on the tibiotalar joint surface in the lateral collateral ligament injury model was concentrated on the posterior-lateral and posterior-medial regions, whereas in the combined injury model, stress on the tibiotalar joint surface was predominantly concentrated in the posterior-medial region. Talus stress was localized to the talus neck and body in all the models, with the combined injury model showing the largest talus displacement (8.46 mm). In the external rotation stress test, stress on the tibiotalar joint surface was mainly distributed in the posterior-medial, posterior-lateral, and anterior-lateral regions in all the models. Talus stress was concentrated at the talus neck and body. The combined injury model exhibited the greatest talus displacement (12.50 mm).Conclusion:Ankle instability, particularly from combined injuries of the distal tibiofibular syndesmosis and lateral collateral ligament, significantly increases the stress concentration and talus displacement under loading conditions, thus elevating the risk of OLT.